In adult "higher" vertebrates, including humans, spinal cord injury can result in permanent behavioral deficits because of very limited axonal regeneration in the CNS and, therefore, this condition remains a serious medical problem. The long-term goals of my research are to understand the cellular and molecular mechanisms that control axonal regeneration of descending brain neurons and recovery of locomotor function after spinal cord injury. The lamprey, a "lower" vertebrate, displays dramatic behavioral recovery after spinal cord transection and has many experimental advantages for examining the mechanisms that control functional axonal regeneration. The present study will investigate five important aspects of axonal regeneration and restoration of locomotor function in spinal cord-transected larval lamprey. (I) (a) Anatomical experiments with lamprey of different ages will test whether some descending brain-spinal cord projections are added during larval life and potentially could contribute to behavioral recovery after spinal cord injury. (b,c) Double labeling will be used to determine if unidentified descending and ascending propriospinal neurons regenerate their axons after spinal cord transection. (II-IV) There are a number of mechanisms that potentially could impact on axonal regeneration and recovery of function, and a better understanding of these mechanisms might lead to methods for enhancing recovery. (II) Intracellular recordings will test whether spinal cord transection results in temporary retraction of synaptic inputs to axotomized descending brain neurons that might compromise sensory-evoked locomotion, particularly at early recovery times. (III) Anatomical experiments will test several mechanisms that might be responsible for different capacities of axonal regeneration of descending brain neurons. (IV) Anatomical and neurophysiological experiments will test the hypothesis that axonal regeneration of descending brain neurons is incomplete because axons grow across a spinal lesion and make synapses, which suppress further regeneration. (V) The hypothesis will be tested that regenerative capacities of axotomized descending brain neurons are not fixed but can be enhanced by a prior "conditioning" spinal cord lesion. Together, these experiments will provide timely and important information that will begin to elucidate the mechanisms that control neural regeneration and behavioral recovery after spinal cord injury in a model vertebrate system.